1. Field of the Invention
The present invention relates to a test device, and method for its use, for detecting the presence of a constituent in a test sample. Moreover, it relates to minimizing the adverse effects of misuse of the device, thereby enhancing its accuracy and dependability.
2. Discussion of the Prior Art
The art of analytical chemistry has been greatly advanced since biochemistry began emerging as a primary scientific frontier requiring increasingly sophisticated analytical methods and tools to solve problems, the solutions to which were never before attempted. Likewise, the medical profession has lent impetus to the growth of analytical chemistry, requiring both high precision and speed in obtaining results. This remarkable progress has been still further spurred by industries such as brewing, chemical manufacturing, and others.
To satisfy the needs of these expanding technologies, a myriad of analytical procedures, compositions and apparatuses have evolved, including solution chemistry techniques, automated machinery and the so-called "dip-and-read" reagent strips. It is to the last of these that the present invention is primarily directed, although substantial benefit ultimately attaches to the other procedures as well.
Reagent strip test devices enjoy wide use in many analytical applications, especially in the chemical analysis of biological fluids, because of their relatively low cost, ease of utilizability and speed in obtaining results. In medicine, for example, numerous physiological functions can be monitored merely by dipping reagent strips into a sample of body fluid, such as urine, and observing a detectable response such as a change in color or a change in the amount of light reflected from or absorbed by the strip.
Compatible with such "dip-and-read" reagent strips have arisen many chemistries for detecting body fluid components. Many of these produce a detectable response which is quantitative or at least semi-quantitative. Thus, by measuring the response after a predetermined time, the analyst can obtain not only a positive indication of the presence of a particular constituent in a test sample, but also an estimate of how much of the constituent is present. Hence, such strips provide the physician with a facile diagnostic tool as well as the ability to gauge the extent of disease or bodily malfunction.
Illustrative of such strips currently in use are products available from the Ames Company Division of Miles Laboratories, Inc. under the trademarks CLINISTIX.RTM., MULTISTIX.RTM., KETOSTIX.RTM., N-MULTISTIX.RTM., DIASTIX.RTM., DEXTROSTIX.RTM., and others. Test devices such as these usually comprise one or more carrier matrices, such as absorbent paper, having incorporated with them a particular reagent or reactant system which manifests a color change in the presence of a specific test sample component. Depending on the reactant system incorporated with a particular matrix, these devices can detect the presence of glucose, ketone bodies, bilirubin, urobilinogen, occult blood, nitrite, and other substances. The specific color change and the intensity of the color observed within a specific time range after contacting the strip with the sample is indicative of the presence of a particular component and its concentration in the sample. Some of these test devices and their reactant systems are set forth in U.S. Pat. Nos. 3,123,443 (CLINISTIX.RTM.); 3,212,855 (KETOSTIX.RTM.); 3,814,668, 3,164,543 and 2,981,606 (DIASTIX.RTM.); and 3,298,789, 3,092,465, 3,164,534 and 2,981,606 (DEXTROSTIX.RTM.).
It is to those of the above-described devices having more than one reagent-bearing carrier matrix that the present invention is primarily applicable. Thus, a reagent strip can contain tests for more than one constituent in a particular liquid sample. For example, a single reagent strip could consist of a reagent-bearing carrier matrix responsive to glucose in urine, and another matrix adjacent the first responsive to ketones, such as acetoacetate. Such a product is marketed by Ames Company under the name KETO-DIASTIX.RTM.. Another reagent strip marketed by Ames Company, N-MULTISTIX.RTM., contains 8 adjacent reagent areas and provides analytical measurements of pH, protein, glucose, ketones, bilirubin, occult blood, nitrite and urobilinogen.
Despite the obvious, time-provded advantages of such multiple reagent strips as these, misuse can result in misinformation. These multiple-analysis tools comprise complex chemical and catalytic systems, each reagent area containing a unique reactive system, responsive to its particular analysate. Thus it is possible, if the reagent strip is misused, for chemicals to be transported by the liquid sample being analyzed from one carrier matrix on the strip to another. Should this happen it is possible for reagents from one carrier matrix to interfere with those of the others so contacted, causing unreliable results. Although it is common in the reagent strip industry to provide detailed instructions as to how this problem is avoided, i.e., directions for using the reagent strips, nevertheless ignorance or disregard of these instructions could permit reagents from one test area to run off onto an adjacent test area. It is to the prevention of this "run-off" problem that the present invention is primarily directed.
The solution of the run-off problem has been long sought after, but, until the advent of the present invention, never found. This solution which applicants discovered was the culmination of an extensive research effort based on their initial conception of how to avoid run-off interference, and the results are indeed unique.
Basically, it was discovered that a certain conformation of a multi-layered carrier matrix, if properly constructed, could dramatically reduce run-off interference in multiple-test reagent strips, even if the instructions for proper use of the strip were not precisely followed.
Whereas the multilayer carrier matrix which applicants invented is truly unique in the analytical arts, it can be said with certainty that multilayer matrices per se have long existed in reagent strips. U.S. Pat. No. 3,531,254 is representative of a group of patents wherein multiple layers are used for the purpose of separating reagents used in a single test. Thus potentially incompatible reagents can be impregnated into separate layers to permit extended storage periods before use. When such a multi-layered matrix is wetted with a test sample, these layers then communicate, and the reagents previously separated become mixed to give the desired analytical test.
Another example of a multi-layered carrier matrix is the one shown in U.S. Pat. No. 3,802,842. Here, a porous pad containing no reagents abuts an upper pad containing the reagents for the desired test. Thus, when liquid sample is applied to such a carrier matrix some of the sample is absorbed by the non-impregnated pad, and some by the one bearing the reagents. As in the previous patent, the layers of this carrier matrix communicate with one another when wet. Some of the liquid (and some of the reagents) pass through the upper pad into the lower pad. There is no barrier provided between the two pads.
There exist other patents which, although less pertinent than the previous two, nevertheless are of interest when considering the present invention, and are mentioned here for the convenience and information of those interested in the present teachings. U.S. Pat. No. 3,418,083 depicts an indicator-impregnated absorbent carrier matrix treated with wax, oil or similar "hydrophobic" agents. It is said that when a sample of blood is placed on such a reagent strip, only the colorless liquid components permeate it, the proteinaceous, colored blood components remaining on the surface where they can be removed. Thus, it is taught, the liquid portion bearing the analysate permeates the reagent pad, whereas colored interferants are precluded from it.
Still another prior art reference, U.S. Pat. No. 3,672,845 assigned to the present assignee, shows spraying adhesive onto a plastic or paper support member for the purpose of gluing on reagent-laden polymer particles. Yet another, U.S. Pat. No. 3,992,158, teaches an upper, semi-permeable layer containing ascorbate oxidase affixed to a lower, reagent-laden layer.
Although none of the aforementioned patents deals in any way with the run-off problem or applicants' solution of it, they represent the present extent of the applicants' knowledge of what is deemed to be the prior art most pertinent to their invention.